MXPA02012688A - Modificacion de glicosilacion de proteina en pichia pastoris. - Google Patents
Modificacion de glicosilacion de proteina en pichia pastoris.Info
- Publication number
- MXPA02012688A MXPA02012688A MXPA02012688A MXPA02012688A MXPA02012688A MX PA02012688 A MXPA02012688 A MX PA02012688A MX PA02012688 A MXPA02012688 A MX PA02012688A MX PA02012688 A MXPA02012688 A MX PA02012688A MX PA02012688 A MXPA02012688 A MX PA02012688A
- Authority
- MX
- Mexico
- Prior art keywords
- genetically engineered
- pichia pastoris
- protein glycosylation
- present
- glycosylation modification
- Prior art date
Links
Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/005—Glycopeptides, glycoproteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/14—Fungi; Culture media therefor
- C12N1/16—Yeasts; Culture media therefor
- C12N1/165—Yeast isolates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
- C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
- C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
- C12N15/815—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts for yeasts other than Saccharomyces
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2477—Hemicellulases not provided in a preceding group
- C12N9/2488—Mannanases
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/0102—Alpha-glucosidase (3.2.1.20)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01024—Alpha-mannosidase (3.2.1.24)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/645—Fungi ; Processes using fungi
- C12R2001/84—Pichia
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Botany (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
Abstract
La presente invencion proporciona cepas geneticamente disenadas de Pichia capaces de producir proteinas con glicosilacion reducida. En particular, las cepas geneticamente disenadas de la presente invencion son capaces de expresar cualquiera o ambas de a-1,2- manosidasa y glucosidasa II. Las cepas geneticamente disenadas de la presente invencion pueden ademas modificarse de tal forma que el OCH1 se rompe. Tambien se proporcionan los metodos para producir glicoproteinas con glicosilacion reducida utilizando tales cepas geneticamente disenadas de Pichia.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US21567600P | 2000-06-30 | 2000-06-30 | |
PCT/IB2001/001514 WO2002000856A2 (en) | 2000-06-30 | 2001-06-29 | Protein glycosylation modification in pichia pastoris |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA02012688A true MXPA02012688A (es) | 2004-09-10 |
Family
ID=22803912
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
MXPA02012688A MXPA02012688A (es) | 2000-06-30 | 2001-06-29 | Modificacion de glicosilacion de proteina en pichia pastoris. |
Country Status (13)
Country | Link |
---|---|
US (4) | US6803225B2 (es) |
EP (3) | EP1294910B1 (es) |
JP (1) | JP4092194B2 (es) |
KR (1) | KR100820367B1 (es) |
AT (1) | ATE414778T1 (es) |
AU (2) | AU7765801A (es) |
CA (1) | CA2411968C (es) |
DE (1) | DE60136623D1 (es) |
DK (1) | DK1294910T3 (es) |
ES (1) | ES2316462T3 (es) |
MX (1) | MXPA02012688A (es) |
PT (1) | PT1294910E (es) |
WO (1) | WO2002000856A2 (es) |
Families Citing this family (52)
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US7625756B2 (en) | 2000-06-28 | 2009-12-01 | GycoFi, Inc. | Expression of class 2 mannosidase and class III mannosidase in lower eukaryotic cells |
DK1297172T3 (da) | 2000-06-28 | 2006-02-13 | Glycofi Inc | Fremgangsmåder til frembringelse af modificerede glucoproteiner |
US7598055B2 (en) | 2000-06-28 | 2009-10-06 | Glycofi, Inc. | N-acetylglucosaminyltransferase III expression in lower eukaryotes |
US7863020B2 (en) | 2000-06-28 | 2011-01-04 | Glycofi, Inc. | Production of sialylated N-glycans in lower eukaryotes |
US7449308B2 (en) | 2000-06-28 | 2008-11-11 | Glycofi, Inc. | Combinatorial DNA library for producing modified N-glycans in lower eukaryotes |
EP1294910B1 (en) | 2000-06-30 | 2008-11-19 | VIB vzw | Protein glycosylation modification in pichia pastoris |
NZ533868A (en) | 2001-12-27 | 2008-09-26 | Glycofi Inc | Methods to engineer mammalian-type carbohydrate structures |
DE60303591T2 (de) | 2002-03-07 | 2007-03-01 | Eidgenössische Technische Hochschule Zürich | System und methode zur herstellung von rekombinanten, glykosylierten protein in prokaryontischen wirtszellen |
US7972809B2 (en) | 2002-04-26 | 2011-07-05 | National Institute Of Advanced Industrial Science & Technology | Methylotrophic yeast producing mammalian type sugar chain |
ITRM20020287A1 (it) * | 2002-05-22 | 2003-11-24 | Univ Roma | Cellule di lievito ingegnerizzate per la produzione di proteine ricombinanti. |
IL165717A0 (en) | 2002-06-26 | 2006-01-15 | Flanders Interuniversity Inst | A strain of methylotrophic yeast for producing proteins |
WO2004003205A1 (en) * | 2002-06-29 | 2004-01-08 | Korea Research Institute Of Bioscience And Biotechnology | Hansenula polymorpha mutant strains with defect in outer chain biosynthesis and the production of recombinant glycoproteins using the same strains |
US7332299B2 (en) | 2003-02-20 | 2008-02-19 | Glycofi, Inc. | Endomannosidases in the modification of glycoproteins in eukaryotes |
CA2518580A1 (en) | 2003-03-12 | 2004-09-23 | Vib Vzw | Improved protein secretion in eukaryotic cells |
US7507573B2 (en) * | 2003-11-14 | 2009-03-24 | Vib, Vzw | Modification of protein glycosylation in methylotrophic yeast |
KR100604994B1 (ko) | 2004-01-30 | 2006-07-26 | 한국생명공학연구원 | 알파1,6-만노실트랜스퍼라제를 코딩하는 한세눌라폴리모르파 기원의 신규 유전자 및 상기 유전자가 결손된한세눌라 폴리모르파 변이주를 이용한 재조합 당단백질생산 방법 |
WO2006024972A2 (en) * | 2004-07-22 | 2006-03-09 | Glycofi, Inc | Malate synthase regulatory sequences for heterologous gene expression in pichia |
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KR101855380B1 (ko) | 2009-11-19 | 2018-05-08 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 원핵세포에서 면역원성 폴리사카라이드를 제조하는 생합성 시스템 |
CA2798381C (en) | 2010-05-06 | 2020-10-06 | Glycovaxyn Ag | Capsular gram-positive bacteria bioconjugate vaccines |
US9187552B2 (en) | 2010-05-27 | 2015-11-17 | Merck Sharp & Dohme Corp. | Method for preparing antibodies having improved properties |
CA2806148A1 (en) | 2010-07-30 | 2012-02-02 | Glycode | A yeast artificial chromosome carrying the mammalian glycosylation pathway |
CA2812870C (en) | 2010-09-29 | 2020-06-09 | Oxyrane Uk Limited | Mannosidases capable of uncapping mannose-1-phospho-6-mannose linkages and demannosylating phosphorylated n-glycans and methods of facilitating mammalian cellular uptake of glycoproteins |
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TWI537385B (zh) | 2010-11-04 | 2016-06-11 | 中央研究院 | 產生具簡單醣基化之表面蛋白質之病毒顆粒的方法 |
EP2895592A1 (en) | 2011-03-23 | 2015-07-22 | Société Industrielle Limousine d'Application Biologique (SILAB) | A yeast recombinant cell capable of producing gdp-fucose |
KR20140028013A (ko) | 2011-05-25 | 2014-03-07 | 머크 샤프 앤드 돔 코포레이션 | 개선된 특성을 갖는 Fc-함유 폴리펩티드를 제조하는 방법 |
CN104024849A (zh) | 2011-08-12 | 2014-09-03 | 生命科技公司 | 用于高通量聚糖分析的装置、方法、计算机程序产品和试剂盒 |
JP6194324B2 (ja) | 2012-03-15 | 2017-09-06 | オキシレイン ユーケー リミテッド | ポンペ病の処置のための方法および材料 |
US9707276B2 (en) | 2012-12-03 | 2017-07-18 | Merck Sharp & Dohme Corp. | O-glycosylated carboxy terminal portion (CTP) peptide-based insulin and insulin analogues |
WO2014093240A1 (en) | 2012-12-10 | 2014-06-19 | The General Hospital Corporation | Bivalent il-2 fusion toxins |
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US9689016B2 (en) * | 2013-12-18 | 2017-06-27 | Caliber Biotherapeutics, Llc | Method for in vivo production of deglycosylated recombinant proteins used as substrate for downstream protein glycoremodeling |
AU2015293949B2 (en) * | 2014-07-21 | 2019-07-25 | Teknologian Tutkimuskeskus Vtt Oy | Production of glycoproteins with mammalian-like N-glycans in filamentous fungi |
CN107205432A (zh) | 2014-11-11 | 2017-09-26 | 克莱拉食品公司 | 用于生成卵清蛋白的方法和组合物 |
AU2019325329A1 (en) * | 2018-08-21 | 2021-04-08 | Clara Foods Co. | Modification of protein glycosylation in microorganisms |
CN109797115B (zh) * | 2019-01-12 | 2022-07-12 | 贵州大学 | 一株产纳豆激酶和β-葡萄糖苷酶解淀粉芽孢杆菌GZU05及其应用方法 |
CN110438027B (zh) * | 2019-06-05 | 2022-08-26 | 贵州大学 | 产多种酶类的解淀粉芽孢杆菌菌株gutu06及其筛选方法 |
EP3997118A4 (en) | 2019-07-11 | 2023-07-19 | Clara Foods Co. | PROTEIN COMPOSITIONS AND CONSUMABLE PRODUCTS THEREOF |
US10927360B1 (en) | 2019-08-07 | 2021-02-23 | Clara Foods Co. | Compositions comprising digestive enzymes |
WO2024032891A1 (en) | 2022-08-11 | 2024-02-15 | Vib Vzw | Glyco-engineered yeast for therapeutic protein production |
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DK1297172T3 (da) | 2000-06-28 | 2006-02-13 | Glycofi Inc | Fremgangsmåder til frembringelse af modificerede glucoproteiner |
EP1294910B1 (en) * | 2000-06-30 | 2008-11-19 | VIB vzw | Protein glycosylation modification in pichia pastoris |
IL165717A0 (en) * | 2002-06-26 | 2006-01-15 | Flanders Interuniversity Inst | A strain of methylotrophic yeast for producing proteins |
WO2004003205A1 (en) | 2002-06-29 | 2004-01-08 | Korea Research Institute Of Bioscience And Biotechnology | Hansenula polymorpha mutant strains with defect in outer chain biosynthesis and the production of recombinant glycoproteins using the same strains |
US7507573B2 (en) * | 2003-11-14 | 2009-03-24 | Vib, Vzw | Modification of protein glycosylation in methylotrophic yeast |
US8270413B2 (en) | 2005-11-28 | 2012-09-18 | Cisco Technology, Inc. | Method and apparatus for self-learning of VPNS from combination of unidirectional tunnels in MPLS/VPN networks |
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2001
- 2001-06-29 EP EP01955499A patent/EP1294910B1/en not_active Revoked
- 2001-06-29 WO PCT/IB2001/001514 patent/WO2002000856A2/en active Application Filing
- 2001-06-29 AT AT01955499T patent/ATE414778T1/de active
- 2001-06-29 JP JP2002506172A patent/JP4092194B2/ja not_active Expired - Lifetime
- 2001-06-29 MX MXPA02012688A patent/MXPA02012688A/es active IP Right Grant
- 2001-06-29 EP EP08019986A patent/EP2028275A3/en not_active Withdrawn
- 2001-06-29 AU AU7765801A patent/AU7765801A/xx active Pending
- 2001-06-29 EP EP10011501A patent/EP2267135A3/en not_active Withdrawn
- 2001-06-29 PT PT01955499T patent/PT1294910E/pt unknown
- 2001-06-29 ES ES01955499T patent/ES2316462T3/es not_active Expired - Lifetime
- 2001-06-29 DK DK01955499T patent/DK1294910T3/da active
- 2001-06-29 AU AU2001277658A patent/AU2001277658B2/en not_active Expired
- 2001-06-29 CA CA002411968A patent/CA2411968C/en not_active Expired - Lifetime
- 2001-06-29 KR KR1020027018059A patent/KR100820367B1/ko active IP Right Grant
- 2001-06-29 DE DE60136623T patent/DE60136623D1/de not_active Expired - Lifetime
- 2001-06-29 US US09/896,594 patent/US6803225B2/en not_active Expired - Lifetime
-
2003
- 2003-09-25 US US10/672,484 patent/US8354268B2/en not_active Expired - Lifetime
-
2009
- 2009-04-16 US US12/424,924 patent/US8663971B2/en not_active Expired - Fee Related
-
2014
- 2014-01-10 US US14/152,329 patent/US9359628B2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
US9359628B2 (en) | 2016-06-07 |
EP2028275A2 (en) | 2009-02-25 |
US8354268B2 (en) | 2013-01-15 |
US20040038381A1 (en) | 2004-02-26 |
KR20030074117A (ko) | 2003-09-19 |
EP1294910B1 (en) | 2008-11-19 |
JP4092194B2 (ja) | 2008-05-28 |
US20020188109A1 (en) | 2002-12-12 |
JP2004501635A (ja) | 2004-01-22 |
AU7765801A (en) | 2002-01-08 |
CA2411968A1 (en) | 2002-01-03 |
ATE414778T1 (de) | 2008-12-15 |
WO2002000856A3 (en) | 2003-01-03 |
KR100820367B1 (ko) | 2008-04-07 |
US20100267084A1 (en) | 2010-10-21 |
EP2028275A3 (en) | 2009-05-06 |
DK1294910T3 (da) | 2009-03-02 |
US6803225B2 (en) | 2004-10-12 |
EP2267135A3 (en) | 2011-09-14 |
CA2411968C (en) | 2009-12-15 |
US8663971B2 (en) | 2014-03-04 |
PT1294910E (pt) | 2009-02-16 |
AU2001277658B2 (en) | 2006-10-19 |
EP2267135A2 (en) | 2010-12-29 |
ES2316462T3 (es) | 2009-04-16 |
WO2002000856A2 (en) | 2002-01-03 |
DE60136623D1 (de) | 2009-01-02 |
EP1294910A2 (en) | 2003-03-26 |
US20140154738A1 (en) | 2014-06-05 |
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